22
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders

      1 , 1
      American Journal of Psychiatry
      American Psychiatric Association Publishing

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A large body of evidence has demonstrated that exposure to childhood maltreatment at any stage of development can have long-lasting consequences. It is associated with a marked increase in risk for psychiatric and medical disorders. This review summarizes the literature investigating the effects of childhood maltreatment on disease vulnerability for mood disorders, specifically summarizing cross-sectional and more recent longitudinal studies that demonstrate childhood maltreatment is more prevalent and associated with increased risk for first mood episode, episode recurrence, greater comorbidities, and increased risk for suicidal ideation and attempts in individuals with mood disorders. It summarizes the persistent alterations associated with childhood maltreatment, including alterations in the HPA axis and inflammatory cytokines, which may contribute to disease vulnerability and a more pernicious disease course. We discuss several candidate genes and environmental factors, for example alcohol/substance use, that may alter disease vulnerability and illness course and neurobiological associations that may mediate these relationships following childhood maltreatment. Studies provide insight into modifiable mechanisms and provide direction to improve both treatment and prevention strategies.

          Related collections

          Most cited references185

          • Record: found
          • Abstract: found
          • Article: not found

          Adverse childhood experiences and the risk of depressive disorders in adulthood.

          Research examining the association between childhood abuse and depressive disorders has frequently assessed abuse categorically, thus not permitting discernment of the cumulative impact of multiple types of abuse. As previous research has documented that adverse childhood experiences (ACEs) are highly interrelated, we examined the association between the number of such experiences (ACE score) and the risk of depressive disorders. Retrospective cohort study of 9460 adult health maintenance organization members in a primary care clinic in San Diego, CA who completed a survey addressing a variety of health-related concerns, which included standardized assessments of lifetime and recent depressive disorders, childhood abuse and household dysfunction. Lifetime prevalence of depressive disorders was 23%. Childhood emotional abuse increased risk for lifetime depressive disorders, with adjusted odds ratios (ORs) of 2.7 [95% confidence interval (CI), 2.3-3.2] in women and 2.5 (95% CI, 1.9-3.2) in men. We found a strong, dose-response relationship between the ACE score and the probability of lifetime and recent depressive disorders (P<0.0001). This relationship was attenuated slightly when a history of growing up with a mentally ill household member was included in the model, but remained significant (P<0.001). The number of ACEs has a graded relationship to both lifetime and recent depressive disorders. These results suggest that exposure to ACEs is associated with increased risk of depressive disorders up to decades after their occurrence. Early recognition of childhood abuse and appropriate intervention may thus play an important role in the prevention of depressive disorders throughout the life span.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions.

            Although the fact that genetic predisposition and environmental exposures interact to shape development and function of the human brain and, ultimately, the risk of psychiatric disorders has drawn wide interest, the corresponding molecular mechanisms have not yet been elucidated. We found that a functional polymorphism altering chromatin interaction between the transcription start site and long-range enhancers in the FK506 binding protein 5 (FKBP5) gene, an important regulator of the stress hormone system, increased the risk of developing stress-related psychiatric disorders in adulthood by allele-specific, childhood trauma-dependent DNA demethylation in functional glucocorticoid response elements of FKBP5. This demethylation was linked to increased stress-dependent gene transcription followed by a long-term dysregulation of the stress hormone system and a global effect on the function of immune cells and brain areas associated with stress regulation. This identification of molecular mechanisms of genotype-directed long-term environmental reactivity will be useful for designing more effective treatment strategies for stress-related disorders.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The link between childhood trauma and depression: insights from HPA axis studies in humans.

              Childhood trauma is a potent risk factor for developing depression in adulthood, particularly in response to additional stress. We here summarize results from a series of clinical studies suggesting that childhood trauma in humans is associated with sensitization of the neuroendocrine stress response, glucocorticoid resistance, increased central corticotropin-releasing factor (CRF) activity, immune activation, and reduced hippocampal volume, closely paralleling several of the neuroendocrine features of depression. Neuroendocrine changes secondary to early-life stress likely reflect risk to develop depression in response to stress, potentially due to failure of a connected neural circuitry implicated in emotional, neuroendocrine and autonomic control to compensate in response to challenge. However, not all of depression is related to childhood trauma and our results suggest the existence of biologically distinguishable subtypes of depression as a function of childhood trauma that are also responsive to differential treatment. Other risk factors, such as female gender and genetic dispositions, interfere with components of the stress response and further increase vulnerability for depression. Similar associations apply to a spectrum of other psychiatric and medical disorders that frequently coincide with depression and are aggravated by stress. Taken together, this line of evidence demonstrates that psychoneuroendocrine research may ultimately promote optimized clinical care and help prevent the adverse outcomes of childhood trauma.
                Bookmark

                Author and article information

                Journal
                American Journal of Psychiatry
                AJP
                American Psychiatric Association Publishing
                0002-953X
                1535-7228
                January 01 2020
                January 01 2020
                : 177
                : 1
                : 20-36
                Affiliations
                [1 ]Department of Psychiatry, Institute of Early Life Adversity Research, and Mulva Clinic for Neuroscience, Dell Medical School, University of Texas, Austin (Lippard, Nemeroff); Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin (Lippard, Nemeroff); and Department of Psychology, University of Texas, Austin (Lippard).
                Article
                10.1176/appi.ajp.2019.19010020
                6939135
                31537091
                6b4ba189-a18d-495d-82cb-42923053d747
                © 2020
                History

                Comments

                Comment on this article